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Publication : Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke.

First Author  Chen ZL Year  2013
Journal  J Cell Biol Volume  202
Issue  2 Pages  381-95
PubMed ID  23857767 Mgi Jnum  J:201512
Mgi Id  MGI:5514280 Doi  10.1083/jcb.201212032
Citation  Chen ZL, et al. (2013) Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke. J Cell Biol 202(2):381-95
abstractText  Astrocytes express laminin and assemble basement membranes (BMs) at their endfeet, which ensheath the cerebrovasculature. The function of astrocytic laminin in cerebrovascular integrity is unknown. We show that ablation of astrocytic laminin by tissue-specific Cre-mediated recombination disrupted endfeet BMs and led to hemorrhage in deep brain regions of adult mice, resembling human hypertensive hemorrhage. The lack of astrocytic laminin led to impaired function of vascular smooth muscle cells (VSMCs), where astrocytes have a closer association with VSMCs in small arterioles, and was associated with hemorrhagic vessels, which exhibited VSMC fragmentation and vascular wall disassembly. Acute disruption of astrocytic laminin in the striatum of adult mice also impaired VSMC function, indicating that laminin is necessary for VSMC maintenance. In vitro, both astrocytes and astrocytic laminin promoted brain VSMC differentiation. These results show that astrocytes regulate VSMCs and vascular integrity in small vessels of deep brain regions. Therefore, astrocytes may be a possible target for hemorrhagic stroke prevention and therapy.
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